The endothelin (ET) family of peptides have potent vascular, cardiac and renal actions which may be of pathophysiological importance in congestive heart failure (CHF). In vivo studies with selective and non-selective ET receptor antagonists are required to clarify the role of ET in the pathophysiology of CHF and determine whether anti-ET drugs may be therapeutically useful in CHF. The impact of angiotensin converting enzyme (ACE) inhibitors on the management of CHF has been such that for any new treatment to be of value it will probably have to offer hemodynamic benefit over and above that already obtained with an ACE inhibitor; anti-ET agents seem to have this potential. The recent formal cloning and characterization of endothelin converting enzyme (ECE) should hasten the development of specific and selective ECE inhibitors and thus provide an alternative investigative, and perhaps therapeutic, tool. Morbidity and mortality from CHF remain unacceptably high even in patients receiving maximal medical therapy, including an ACE inhibitor. Blockade of either the generation (through ECE inhibition) or actions (through receptor blockade) of ET warrant further investigation as potential new therapeutic strategies.